Respiratory syncytial virus: A new era / Virus respiratorio sincitial: un nuevo tiempo

Respiratory syncytial virus (RSV) is a major public health problem that has undergone significant changes in recent years. First of all, it has become easier to diagnose with highly reliable and rapidly available confirmatory tests. This has led to a better understanding of its epidemiology and RSV has gone from being a disease of the pediatric age group, severe only in infants and immunosuppressed children, to being a common disease in people of all ages, particularly important in patients of advanced age or with immunosuppressive diseases. Recent therapeutic and prophylactic advances, both with long-lasting monoclonal antibodies and vaccines, are another reason for satisfaction. For these reasons, the COVID and Emerging Pathogens Committee of the Illustrious Official College of Physicians of Madrid (ICOMEM) has considered it pertinent to review this subject in the light of new knowledge and new resources for dealing with this infection. We have formulated a series of questions that we believe will be of interest not only to members of the College but also to any non-expert in this subject, with a particular focus on the situation of RSV infection in Spain. (AU)

El Virus Respiratorio Sincitial (VRS), es un problema de salud pública de primera magnitud que en años recientes ha experimentado cambios muy importantes. En primer lugar, se ha producido una mayor facilidad diagnóstica con pruebas confirmatorias altamente fiables y rápidamente disponibles. Esto ha permitido conocer mejor su epidemiología y VRS ha pasado de ser una enfermedad de la edad pediátrica, grave sólo en lactantes y niños inmunodeprimidos, a ser una enfermedad común en personas de toda edad, particularmente importante en pacientes de edades avanzadas o con enfermedades que inmunodeprimen. Los avances terapéuticos y profilácticos, recientes, tanto con anticuerpos monoclonales de larga duración como con vacunas, constituyen otro motivo de satisfacción. Por estos motivos, el Comité de COVID y de patógenos emergentes del Ilustre Colegio Oficial de Médicos de Madrid (ICOMEM) ha considerado pertinente revisar este tema, a la luz de los nuevos conocimientos y de los nuevos recursos para afrontar esta infección. Hemos formulado una serie de preguntas que creemos de interés no sólo para los colegiados si no para cualquier persona no experta en este tema, con una vista particular en la situación de la infección por VRS en España. (AU)

Analysis of retreatment with monoclonal antibodies in chronic/episodic migraine: Real world data.

OBJECTIVE: To analyze the response to retreatment in patients with chronic/episodic migraine who discontinued therapy with erenumab/fremanezumab after 1 year of treatment. METHODS: Observational, retrospective, single-center, multidisciplinary study in patients with chronic/episodic migraine who received therapy with erenumab/fremanezumab for at least 1 year and discontinued it after achieving an adequate response (optimization). The evaluation of the response after retreatment included the following variables: DMM, MIDAS, and HIT-6 scales at the beginning of retreatment and 3 months later. The response was evaluated in different subgroups (episodic/chronic, erenumab/fremanezumab, and time until retreatment). RESULTS: 48 patients were included. 70.8% (n=34) required retreatment with mAb, with a median of 3.9 (2.9-6.4) months until reintroduction. Clinical response after retreatment was achieved in 67.6% (n=23) of patients. No statistically significant differences were found in the analyzed subgroups. CONCLUSION: Interruption of treatment with erenumab/fremanezumab for chronic/episodic migraine produces a clinical worsening of the disease requiring retreatment in most cases, approximately after 4 months. Two out of three patients respond positively after restarting monoclonal therapy. This response does not appear to be related to the type of migraine, the specific monoclonal antibody prescribed, or the time to retreatment.

Estudio tecnofarmacéutico de los Anticuerpos Conjugados a Fármacos comercializados en España / Technopharmaceutical study of antibodies drug conjugated marketed in Spain

Introducción: el tratamiento del cáncer supone uno de los grandes desafíos a los que se enfrenta la sociedad cien-tífica actual. En esta lucha sanitaria, se desarrollan los anticuerpos conjugados a fármacos, capaces de lograr la muerte celular mediante el transporte y liberación de compuestos citotóxicos selectivamente sobre células tumorales. Se componen de un anticuerpo monoclonal (de naturaleza proteica) unido a un fármaco citotóxico (de carácter lipófilo) mediante un enlazador. Las formulaciones se han de diseñar para mantener dicha unión durante su almacenamiento y administración. Objetivo: identificar los medicamentos comercializados en España cuyo principio activo es un anticuerpo conjugado a fármaco, estudiando diferentes aspectos tecnofarmacéuticos, en especial los componentes de sus formulaciones. Método: dado que este tipo de medicamento pertenece al grupo ATC L01F, han sido identificados a través del bus-cador de la Agencia Española de Medicamentos y Productos Sanitarios. La consulta de sus fichas técnicas, artículos de revisión e investigación relacionados con el tema así como el Handbook of Pharmaceuticals Excipients, ha permitido realizar el estudio tecnofarmacéutico. Resultados: se han analizado distintos aspectos tecnofarmacéuticos: forma farmacéutica, vía de administración, conservación y, en especial, sus formulaciones. Se ha estudiado en profundidad la naturaleza del principio activo y los requisitos de las formulaciones en base a sus características. Conclusiones: los ocho anticuerpos conjugados a fármacos aprobados en España se presentan en forma de polvo liofilizado en vial que se deben almacenar entre 2-8 ºC. Para su administración, se reconstituyen obteniéndose inicialmente un concentrado, que posteriormente se diluye y administra en forma de perfusión intravenosa o goteo. Su formulación tipo incluye un lioprotector, un antiagregante, un regulador del pH y eventualmente antioxidantes o reductores de la viscosidad. (AU)

Introduction: cancer treatment is one of the great challenges facing today’s scientific society. In this health fight, drug-conjugated antibodies (ADCs) are being developed, drugs capable of causing cell death by transporting and releasing cytotoxic compounds into tumor cells. They are composed of a monoclonal antibody (of protein nature) linked to a cytotoxic drug (of lipophilic character) through a linker. Formulations must be designed to maintain this binding during storage and administration.Objective: identify the medicines marketed in Spain whose active ingredient is an antibody-drug conjugate, studying techno pharmaceutical aspects, especially the components of their formulations. Method: since this type of drugs belongs to the ATC group L01F, they have been identified through the search engine of the Spanish Agency of Medicines and Health Products. The search for their technical sheets, along with articles of review and research related to the topic, as well as the Handbook of Pharmaceuticals Excipients, has enabled the execution of the techno pharmaceutical study.the formulation of the tested conjugates to drugs marketed in Spain belonging to the ATC L01F group corresponding to “monoclonal antibodies and tested conjugated to drugs” identified through the search engine of the Spanish Agency of Medicines and Health Products has been studied. Results: different aspects of this group of drugs have been analyzed, such as the pharmaceutical form, the route of administration, conservation and especially the techno pharmaceutical formulation. The nature of the active ingredient and the requirements of the formulations based on their characteristics have been studied in depth. Conclusions: the eight antibody-drug conjugates approved in Spain are presented in the form of lyophilized powder in a vial and should be stored between 2-8 ºC... (AU)

Farmacocinética de eculizumab en pacientes adultos y pediátricos con síndrome hemolítico urémico atípico y glomerulopatía C3 / Pharmacokinetics of eculizumab in adult and pediatric patients with atypical hemolytic uremic syndrome and C3 glomerulopathy

Objetivo analizar y describir las concentraciones de eculizumab y el bloqueo del complemento en los pacientes con síndrome hemolítico urémico atípico (SHUa) y glomerulopatía C3, y definir un margen terapéutico donde se alcance una alta probabilidad de conseguir eficacia terapéutica. Métodos estudio observacional, ambispectivo y multicéntrico que incluyó pacientes adultos y pediátricos diagnosticados de SHUa y glomerulopatía C3 desde septiembre de 2020 hasta octubre de 2022 en 5 hospitales de España. Eculizumab se administró a las dosis recomendadas por la ficha técnica. Se determinaron las concentraciones pre y posdosis de eculizumab, así como del bloqueo de la vía clásica del complemento (CH50). Se recogieron variables sociodemográficas, analíticas y clínicas, y se calcularon los parámetros farmacocinéticos. Para establecer el punto de corte de las concentraciones de eculizumab que predecían el bloqueo del complemento se realizó un análisis de curvas ROC (Receiver Operating Characteristic). Se utilizó el test de Kruskal-Wallis para contrastar las diferencias en distintos parámetros según las concentraciones de eculizumab. Resultados se incluyeron 25 pacientes, 19 adultos (76,0%) y 6 pediátricos (24,0%), con edades medianas de 43,4 (RIC 35,7-48,8) y 10,1 (RIC 9,6-11,3) años, respectivamente. De ellos, 22 (88,0%) pacientes fueron diagnosticados con SHUa y 3 (12,0%) con glomerulopatía C3. Se determinaron un total de 111 concentraciones de eculizumab. Las concentraciones predosis y posdosis medias detectadas durante la fase de mantenimiento fueron 243,8 (SD 240,6) μg/ml y 747,4 (SD 444,3) μg/ml, respectivamente (AU)

Objective The objective of the study was to analyze and describe the concentrations of eculizumab and the complement blockade in patients with atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy, and to define a therapeutic margin where there is a high probability of achieving therapeutic efficacy. Methods Observational, ambispective and multicenter study that included adult and pediatric patients diagnosed with aHUS and C3 glomerulopathy from September 2020 to October 2022 in five hospitals in Spain. Eculizumab was administered at the doses recommended by the data sheet according to the European Medicines Agency (EMA). Pre-dose and post-dose concentrations of eculizumab were determined, as well as blockade of the classical complement pathway (CH50). Sociodemographic and clinical data were collected, and pharmacokinetic parameters were calculated. To establish the cut-off point for eculizumab concentrations that predicted complement blockade, Receiver Operating Characteristic (ROC) curve analysis was performed. Lastly, the Kruskal-Wallis test was used to contrast the differences in different parameters according to eculizumab concentrations. Results Twenty-five patients were included, 19 adults (76.0%) and 6 pediatrics (24.0%), with median ages of 43.4 (IQR 35.7-48.8) and 10.1 (IQR 9.6-11.3) years, respectively. Of these, 22 (88.0%) patients were diagnosed with aHUS and 3 (12.0%) with C3 glomerulopathy. A total of 111 eculizumab concentrations were determined (AU)

Percepción de la mujer con psoriasis en la planificación familiar: Estudio descriptivo, transversal y multicéntrico / Family Planning Concerns Among Women With Psoriasis: A Descriptive, Cross-Sectional, Multicenter Study

Antecedentes y objetivos La psoriasis afecta a un gran porcentaje de mujeres en edad fértil. Nuestro objetivo fue conocer las inquietudes de las mujeres con psoriasis en relación con la planificación familiar. Material y métodos Estudio observacional, descriptivo, transversal y multicéntrico realizado entre marzo del 2020 y octubre del 2021. Se recabaron datos sociodemográficos e inquietudes relacionadas con la planificación familiar de mujeres entre 18-45 años con psoriasis en placas y candidatas a recibir tratamiento sistémico. Resultados Se reclutaron 153 pacientes de 11 centros españoles (edad media: 35,4 ± 8 años, duración media de la enfermedad: 16,7 años); 38,4% de los casos tenían una enfermedad moderada/grave para los médicos, aunque la percepción de la actividad era significativamente superior para las pacientes. En una de cada tres mujeres, la enfermedad limitaba o retrasaba el deseo gestacional. Existía preocupación de que la enfermedad empeorara al tener que retirar o cambiar un fármaco o que los tratamientos perjudicaran al bebé. Alrededor de la mitad de las pacientes no había recibido información sobre planificación familiar en la consulta, especialmente aquellas mujeres sin embarazos previos. Las mujeres con tratamiento biológico (58,7%) tenían mejor situación clínica, mejor calidad de vida y menos alteraciones en la esfera sexual que las pacientes sin tratamiento biológico. Conclusiones Las pacientes con psoriasis tienen numerosas preocupaciones relacionadas con la planificación familiar. En algunos casos, estos miedos podrían llevar a retrasar y/o limitar el deseo gestacional. Sería necesario incrementar la información que se da a las pacientes y mejorar la formación de los dermatólogos en este tema (AU)

Background and objective A significant proportion of women of childbearing age have psoriasis. The aim of this study was to examine family planning concerns in this population. Material and methods Observational, descriptive, cross-sectional, multicenter study conducted between March 2020 and October 2021. We collected sociodemographic data and analyzed responses to a family planning questionnaire administered to women aged 18 to 45 years with plaque psoriasis who were candidates for systemic treatment. Results We studied 153 patients (mean [SD] age, 35.4 [8.0] years; mean disease duration, 16.7 years) being treated at 11 Spanish hospitals. Overall, 38.4% of women were considered to have moderate to severe psoriasis by their physicians; perceived severity ratings were significantly higher among women. Psoriasis affected the women's desire to become pregnant or led to their delaying pregnancy in 1 in 3 respondents. They were concerned that their condition might worsen if they had to discontinue or switch treatment or that the treatment might harm the baby. Approximately half of the women had not received family planning counseling from their physicians, and this was more likely to be the case among never-pregnant women. Women on biologic therapy (58.7%) had better psoriasis control and a better quality of life than women on other treatments. Their sexual health was also less affected. Conclusions Women with psoriasis have numerous family planning concerns, which in some cases can lead them to delay pregnancy or affect their desire to become pregnant. Dermatologists need to receive better training regarding family planning in women with psoriasis so that they can provide their patients with more and better information (AU)

[Translated article] Family Planning Concerns Among Women With Psoriasis: A Descriptive, Cross-Sectional, Multicenter Study / Percepción de la mujer con psoriasis en la planificación familiar: estudio descriptivo, transversal y multicéntrico

Background and objective A significant proportion of women of childbearing age have psoriasis. The aim of this study was to examine family planning concerns in this population. Material and methods Observational, descriptive, cross-sectional, multicenter study conducted between March 2020 and October 2021. We collected sociodemographic data and analyzed responses to a family planning questionnaire administered to women aged 18 to 45 years with plaque psoriasis who were candidates for systemic treatment. Results We studied 153 patients (mean [SD] age, 35.4 [8.0] years; mean disease duration, 16.7 years) being treated at 11 Spanish hospitals. Overall, 38.4% of women were considered to have moderate to severe psoriasis by their physicians; perceived severity ratings were significantly higher among women. Psoriasis affected the women's desire to become pregnant or led to their delaying pregnancy in 1 in 3 respondents. They were concerned that their condition might worsen if they had to discontinue or switch treatment or that the treatment might harm the baby. Approximately half of the women had not received family planning counseling from their physicians, and this was more likely to be the case among never-pregnant women. Women on biologic therapy (58.7%) had better psoriasis control and a better quality of life than women on other treatments. Their sexual health was also less affected. Conclusions Women with psoriasis have numerous family planning concerns, which in some cases can lead them to delay pregnancy or affect their desire to become pregnant. Dermatologists need to receive better training regarding family planning in women with psoriasis so that they can provide their patients with more and better information (AU)

Antecedentes y objetivos La psoriasis afecta a un gran porcentaje de mujeres en edad fértil. Nuestro objetivo fue conocer las inquietudes de las mujeres con psoriasis en relación con la planificación familiar. Material y métodos Estudio observacional, descriptivo, transversal y multicéntrico realizado entre marzo del 2020 y octubre del 2021. Se recabaron datos sociodemográficos e inquietudes relacionadas con la planificación familiar de mujeres entre 18-45 años con psoriasis en placas y candidatas a recibir tratamiento sistémico. Resultados Se reclutaron 153 pacientes de 11 centros españoles (edad media: 35,4 ± 8 años, duración media de la enfermedad: 16,7 años); 38,4% de los casos tenían una enfermedad moderada/grave para los médicos, aunque la percepción de la actividad era significativamente superior para las pacientes. En una de cada tres mujeres, la enfermedad limitaba o retrasaba el deseo gestacional. Existía preocupación de que la enfermedad empeorara al tener que retirar o cambiar un fármaco o que los tratamientos perjudicaran al bebé. Alrededor de la mitad de las pacientes no había recibido información sobre planificación familiar en la consulta, especialmente aquellas mujeres sin embarazos previos. Las mujeres con tratamiento biológico (58,7%) tenían mejor situación clínica, mejor calidad de vida y menos alteraciones en la esfera sexual que las pacientes sin tratamiento biológico. Conclusiones Las pacientes con psoriasis tienen numerosas preocupaciones relacionadas con la planificación familiar. En algunos casos, estos miedos podrían llevar a retrasar y/o limitar el deseo gestacional. Sería necesario incrementar la información que se da a las pacientes y mejorar la formación de los dermatólogos en este tema (AU)

[Translated article] Pharmacokinetics of eculizumab in adult and pediatric patients with atypical hemolytic uremic syndrome and C3 glomerulopathy.

OBJECTIVE: The objective of the study was to analyze and describe the concentrations of eculizumab and the complement blockade in patients with atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy, and to define a therapeutic margin where there is a high probability of achieving therapeutic efficacy. METHODS: Observational, ambispective, and multicenter study that included adult and pediatric patients diagnosed with aHUS and C3 glomerulopathy from September 2020 to October 2022 in 5 hospitals in Spain. Eculizumab was administered at the doses recommended by the data sheet according to the European Medicines Agency (EMA). Pre- and post-dose concentrations of eculizumab were determined, as well as blockade of the classical complement pathway (CH50). Sociodemographic and clinical data were collected, and pharmacokinetic parameters were calculated. To establish the cut-off point for eculizumab concentrations that predicted complement blockade, Receiver Operating Characteristic (ROC) curve analysis was performed. Lastly, the Kruskal-Wallis test was used to contrast the differences in different parameters according to eculizumab concentrations. RESULTS: Twenty-five patients were included, 19 adults (76.0%) and 6 pediatrics (24.0%), with median ages of 43.4 (interquartile range (IQR) 35.7-48.8) and 10.1 (IQR 9.6-11.3) years, respectively. Of these, 22 (88.0%) patients were diagnosed with aHUS and 3 (12.0%) with C3 glomerulopathy. A total of 111 eculizumab concentrations were determined. Mean pre- and post-dose concentration values detected during the maintenance phase were 243.8 (SD 240.6) µg/mL and 747.4 (standard deviation (SD) 444.3) µg/mL, respectively. Increased complement blockade was observed at higher pre-dose concentrations (P = .002) and decreased serum creatinine at both higher pre- and post-dose concentrations (P = .001 and P = .017, respectively). Using ROC curves, it was determined that a pre-dose concentration >149.0 µg/mL was optimal to achieve complement blockade, with an AUC of 0.87 (0.78-0.95). Finally, high inter-individual (48.9% variation coefficient (CV)) with low intra-individual variabilities (11.9% CV) in eculizumab clearance were observed. CONCLUSIONS: The present study reports supratherapeutic concentrations of eculizumab in patients with aHUS, and defines higher concentrations than those described in the data sheet to achieve blockade, thus encouraging the personalization of treatment with eculizumab.

[Translated article] Family Planning Concerns Among Women With Psoriasis: A Descriptive, Cross-Sectional, Multicenter Study.

BACKGROUND AND OBJECTIVE: A significant proportion of women of childbearing age have psoriasis. The aim of this study was to examine family planning concerns in this population. MATERIAL AND METHODS: Observational, descriptive, cross-sectional, multicenter study conducted between March 2020 and October 2021. We collected sociodemographic data and analyzed responses to a family planning questionnaire administered to women aged 18 to 45 years with plaque psoriasis who were candidates for systemic treatment. RESULTS: We studied 153 patients (mean [SD] age, 35.4 [8.0] years; mean disease duration, 16.7 years) being treated at 11 Spanish hospitals. Overall, 38.4% of women were considered to have moderate to severe psoriasis by their physicians; perceived severity ratings were significantly higher among women. Psoriasis affected the women's desire to become pregnant or led to their delaying pregnancy in 1 in 3 respondents. They were concerned that their condition might worsen if they had to discontinue or switch treatment or that the treatment might harm the baby. Approximately half of the women had not received family planning counseling from their physicians, and this was more likely to be the case among never-pregnant women. Women on biologic therapy (58.7%) had better psoriasis control and a better quality of life than women on other treatments. Their sexual health was also less affected. CONCLUSIONS: Women with psoriasis have numerous family planning concerns, which in some cases can lead them to delay pregnancy or affect their desire to become pregnant. Dermatologists need to receive better training regarding family planning in women with psoriasis so that they can provide their patients with more and better information.

Family Planning Concerns Among Women With Psoriasis: A Descriptive, Cross-Sectional, Multicenter Study. / Percepción de la mujer con psoriasis en la planificación familiar: Estudio descriptivo, transversal y multicéntrico.

BACKGROUND AND OBJECTIVE: A significant proportion of women of childbearing age have psoriasis. The aim of this study was to examine family planning concerns in this population. MATERIAL AND METHODS: Observational, descriptive, cross-sectional, multicenter study conducted between March 2020 and October 2021. We collected sociodemographic data and analyzed responses to a family planning questionnaire administered to women aged 18 to 45 years with plaque psoriasis who were candidates for systemic treatment. RESULTS: We studied 153 patients (mean [SD] age, 35.4 [8.0] years; mean disease duration, 16.7 years) being treated at 11 Spanish hospitals. Overall, 38.4% of women were considered to have moderate to severe psoriasis by their physicians; perceived severity ratings were significantly higher among women. Psoriasis affected the women's desire to become pregnant or led to their delaying pregnancy in 1 in 3 respondents. They were concerned that their condition might worsen if they had to discontinue or switch treatment or that the treatment might harm the baby. Approximately half of the women had not received family planning counseling from their physicians, and this was more likely to be the case among never-pregnant women. Women on biologic therapy (58.7%) had better psoriasis control and a better quality of life than women on other treatments. Their sexual health was also less affected. CONCLUSIONS: Women with psoriasis have numerous family planning concerns, which in some cases can lead them to delay pregnancy or affect their desire to become pregnant. Dermatologists need to receive better training regarding family planning in women with psoriasis so that they can provide their patients with more and better information.

Pharmacokinetics of eculizumab in adult and pediatric patients with atypical hemolytic uremic syndrome and C3 glomerulopathy. / Farmacocinética de eculizumab en pacientes adultos y pediátricos con síndrome hemolítico urémico atípico y glomerulopatía C3.

OBJECTIVE: The objective of the study was to analyze and describe the concentrations of eculizumab and the complement blockade in patients with atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy, and to define a therapeutic margin where there is a high probability of achieving therapeutic efficacy. METHODS: Observational, ambispective and multicenter study that included adult and pediatric patients diagnosed with aHUS and C3 glomerulopathy from September 2020 to October 2022 in five hospitals in Spain. Eculizumab was administered at the doses recommended by the data sheet according to the European Medicines Agency (EMA). Pre-dose and post-dose concentrations of eculizumab were determined, as well as blockade of the classical complement pathway (CH50). Sociodemographic and clinical data were collected, and pharmacokinetic parameters were calculated. To establish the cut-off point for eculizumab concentrations that predicted complement blockade, Receiver Operating Characteristic (ROC) curve analysis was performed. Lastly, the Kruskal-Wallis test was used to contrast the differences in different parameters according to eculizumab concentrations. RESULTS: Twenty-five patients were included, 19 adults (76.0%) and 6 pediatrics (24.0%), with median ages of 43.4 (IQR 35.7-48.8) and 10.1 (IQR 9.6-11.3) years, respectively. Of these, 22 (88.0%) patients were diagnosed with aHUS and 3 (12.0%) with C3 glomerulopathy. A total of 111 eculizumab concentrations were determined. Mean pre-dose and post-dose concentration values detected during the maintenance phase were 243.8 (SD 240.6) µg/mL and 747.4 (SD 444.3) µg/mL, respectively. Increased complement blockade was observed at higher pre-dose concentrations (p=0.002) and decreased serum creatinine at both higher pre- and post-dose concentrations (p=0.001 and p=0.017, respectively). Using ROC curves, it was determined that a pre-dose concentration >149.0 µg/mL was optimal to achieve complement blockade, with an AUC of 0.87 (0.78-0.95). Finally, high inter-individual (48.9% CV) with low intra-individual variabilities (11.9% CV) in eculizumab clearance were observed. CONCLUSIONS: The present study reports supratherapeutic concentrations of eculizumab in patients with aHUS, and defines higher concentrations than those described in the data sheet to achieve blockade, thus encouraging the personalization of treatment with eculizumab.

Anticuerpos monoclonales biespecíficos: Cuidados de enfermería a propósito de un caso / [Bispecific monoclonal antibodies: Nursing care regarding a case]

El cáncer sigue siendo una enfermedad de primera magnitud a nivel mundial y uno de los pilares para su supervivencia son los tratamientos antineoplásicos. En los últimos años se ha producido un gran avance habiendo descrito múltiples estrategias de desarrollo, para conseguir mayor actividad antitumoral y menor toxicidad. En este contexto cabe destacar el uso de los anticuerpos monoclonales, en concreto, en los anticuerpos monoclonales biespecíficos. Dada la complejidad de estos tipos de tratamientos y sus efectos secundarios, es necesaria la formación en cuidados de enfermería específicos, con profesionales que tengan los conocimientos necesarios para garantizar una vigilancia adecuada a estos pacientes. Es por ello que el objetivo principal de este estudio es generar un Plan de Cuidados de Enfermería a una paciente con diagnóstico de Linfoma B del alto grado, que ha recibido tratamiento con Epcoritamab en el Hospital Universitario de Canarias. Así, en este artículo se realizó una valoración de enfermería según los patrones funcionales de Marjory Gordon y se desarrolló un Plan de Cuidados Individualizado (PCI) centrado en los siguientes diagnósticos: náuseas, patrón respiratorio ineficaz, riesgo de shock y riesgo de confusión aguda. (AU)

[Control de asma grave predominantemente eosinofílica con el uso de anti IL-5].

Background: Asthma is a chronic inflammatory disease of the airways, caused by inflammatory cells and mediators, associated with smooth muscle dysfunction, causing variable airflow obstruction. With high, low and mixed type 2 immunoinflammatory mechanisms (endotypes). Severe asthma is that which requires step 4 or 5 of treatment (GINA 2023). The TH2 High phenotype, non-allergic with eosinophilia and FENO, is the second most common. It affects 300 million people around the world. Objetive: Describe asthma biomarkers after the use of antiinterleukin 5, Benralizumab, in adults with severe asthma. Methods: Case report, descriptive study. Patients with severe eosinophilic asthma and chronic polyposis rhinosinusitis under treatment with anti-IL5 were included, evaluating inflammatory biomarkers. Results: Serum eosinophils, FENO, ACT, spirometry, and exacerbations were measured in 8 patients at baseline and 6 months after treatment. The FEV1-FVC was 51% with improvement up to 95% later. 5 patients had FENO > 45 ppm subsequently only 3 continued to be inflamed. Eosinophilia 150 cells and subsequently only 1 patient persisted with eosinophilia 200 cells. Initial ACT < 19 in 7 patients Final ACT >19 in 7 patients. Exacerbations 8 patients with 2 or more exacerba- tions subsequently only 1 patient presented exacerbation. Conclusion: The use of anti-interleukin 5 (benralizumab) does reduce inflammatory markers, improves control and number of exacerbations in the short term. Monoclonal antibodies (Anti IL-5), if they improve inflammatory biomarkers, if clinical characteristics and inflammatory biomarkers are taken into account, it favors adequate asthma control.

Antecedentes: El asma es una enfermedad inflamatoria crónica de vías respiratorias, provocada por células y mediadores inflamatorios, asociado a disfunción del músculo liso, provocando obstrucción variable del flujo aereo. Con mecanismos inmunoinflamatorios tipo 2 altos, bajos y mixtos (endotipos). Asma grave es aquella que requiere paso 4 o 5 de tratamiento (GINA 2023). El fenotipo TH2 Alto, no alergico con eosinofilia y FENO, es el segundo más común. Afecta a 300 millones de personas alrededor del mundo. Objetivo: Describir biomarcadores de asma, posterior al uso de antiinterleucina 5, Benralizumab, en adultos con asma grave. Métodos: Reporte de casos, estudio descriptivo. Se incluyeron pacientes con asma grave eosinofilica y rinosinusitis crónica poliposica en tratamiento con an- ti-IL5, evaluando biomarcadores inflamatorios Resultados: En 8 pacientes se midieron eosinófilos séricos, FENO, ACT, espirometría y exacerbaciones al inicio y 6 meses después del tratamiento. El FEV1-FVC fue 51% con mejoría hasta 95% después. 5 pacientes tenían FENO >45 ppm posteriormente solo 3 continuron inflamados. Eosinofilia 150 células y posterior- mente solo 1 paciente persistió con eosinofilia 200 células. ACT inicial < 19 en 7 pacientes ACT final > 19 en 7 pacientes. Exacerbaciones 8 pacientes con 2 o más exacerbaciones posteriormente solo 1 paciente presentó exacerbación. Conclusión: El uso de antiinterleucina 5 (Benralizumab) si disminuye marcadores inflamatorios, mejora el control y número de exacerbaciones a corto plazo. Los anticuerpos monoclonales (Anti IL-5), si mejoran biomarcadores inflamatorios si se toman en cuenta caracteristicas clínicas y biomarcadores inflamatorios favorece adecuado control de asma.

[Tezepelumab: a new option for the treatment of severe asthma]. / Tezepelumab: una nueva opción para el tratamiento del asma grave.

In Latin America, asthma is a public health problem with a significant impact on both patients and health systems. The greater understanding of the pathophysiology and the recognition of the central role that inflammation has in the severity of asthma has favored the development of monoclonal antibodies that have IL-5, IL-4, IL-13 and IgE as therapeutic targets. Although these therapeutic alternatives promote better control of the disease, not all patients respond favorably to these treatments. Therefore, it is of particular interest to explore monoclonal antibodies such as Tezepelumab, directed against thymic stromal lymphopoietin (TSLP), an alarmin (epithelial cytokine) that participates in the initiation and perpetuation of inflammation in Asthma. Therefore, in this review, we will show the clinical efficacy of tezepelumab in reducing the annual rate of exacerbations, improving lung function, and reducing bronchial hyperreactivity, regardless of the patient's baseline biomarker levels. Therefore, this new molecule is a highly effective therapeutic option for patients with severe asthma.

En Latinoamérica, el asma es un problema de salud pública con un impacto importante tanto para los pacientes como para los sistemas de salud. El mayor entendimiento de la fisiopatología y el reconocimiento del papel central que tiene la inflamación en la severidad del asma ha favorecido el desarrollo de anticuerpos monoclonales que tienen como blancos terapéuticos a la IL-5, IL-4, IL-13 y la IgE. Si bien estas alternativas terapéuticas favorecen un mejor control de la enfermedad, no todos los pacientes responden favorablemente a esos tratamientos. Por lo que resulta de particular interés explorar anticuerpos monoclonales como el Tezepelumab, dirigido contra la linfopoyetina estromal tímica (TSLP) una alarmina (citocina epitelial) que participa en el inicio y la perpetuación de la inflamación en el Asma. Por lo que, en esta revisión, mostraremos la eficacia clínica del tezepelumab en la disminución de la tasa anual de exacerbaciones, mejora en la función pulmonar y en la disminución en la hiperreactividad bronquial, independientemente de los niveles de biomarcadores basales que el paciente presente. Por lo que esta nueva molécula es una opción terapéutica altamente eficaz para el paciente con asma grave.

Biological therapy, surgery, and hospitalization rates for inflammatory bowel disease: An observational Latin American comparative study between adults and pediatric patients.

OBJECTIVE: Compare the proportions of use of biological therapy, surgeries, and hospitalizations between adults and pediatric inflammatory bowel disease (IBD)-Crohn's disease (CD) and ulcerative colitis (UC)-patients. PATIENTS AND METHODS: Observational, retrospective, and multicenter study. Data were collected from all consecutive IBD patients seen as outpatients or admitted to hospital, during 2015-2021, in two IBD tertiary centers in a South Brazilian capital. Patients with unclassified colitis diagnosis were excluded from this study. Patients were classified as having CD or UC and sub-categorized as adult or pediatric according to age. Data were analyzed using frequency, proportion, Fisher's exact test, and Chi-square test. RESULTS: A total of 829 patients were included: 509 with CD (378 adults/131 pediatric) and 320 with UC (225/95). Among patients with CD, no differences were observed for proportions of use of biological therapy (80.2% in pediatric vs. 73.3% in adults; P=0.129), surgery (46.6% vs. 50.8%; P=0.419), or hospitalization (64.9% vs. 56.9%; P=0.122). In UC, significant differences were observed for biological therapy (40.0% vs. 28.0%; P=0.048) and hospitalization (47.4% vs. 24.0%; P<0.001). No significant difference was observed in surgery rates (17.9% vs. 12.4%; P=0.219). CONCLUSIONS: Biological therapy and incidence of hospitalization were greater among pediatric patients with UC, compared with adults; no difference was observed in the need for abdominal surgery. In CD, no significant difference was observed in the three main outcomes between the age groups.

Evidentia praxis: nirsevimab y prevención de bronquiolitis en lactantes nacidos a término / Evidentia praxis: Nirsevimab and bronchiolitis prevention in term-born infants

Analizamos la evidencia publicada sobre la eficacia y seguridad de nirsevimab, un anticuerpo monoclonal, empleado para prevenir las infecciones de vías respiratorias bajas (IVRB) por virus respiratorio sincitial (VRS) en el lactante a término. Encontramos un ensayo clínico aleatorizado controlado con placebo doble ciego que incluyó 3012 lactantes, nacidos a término o pretérmino tardío, menores de un año con un seguimiento de al menos 150 días. La calidad de la evidencia se clasificó como baja para IVRB muy grave y moderada para IVRB que precisara asistencia o ingreso. La evidencia se sustenta sobre un escaso número de eventos (para ingresos hospitalarios sólo 29 casos, para IVRB con atención médica 78), por lo que cualquier estimación debe considerarse imprecisa. La eficacia, estimada como reducción relativa del riesgo (RRR) fue del 76,4% (intervalo de confianza del 95% [IC 95]: 62,3 a 85,2) para IVRB por VRS y del 76,8% (IC 95: 49,4 a 89,4%) para ingreso. No se encontraron diferencias en cuanto a seguridad. Existen dudas sobre la importancia clínica, por los criterios de gravedad empleados, y sobre su impacto, con un número necesario a tratar para evitar una IVRB con ingreso de 63 y que requiera asistencia médica de 24. Por la información disponible parece una intervención segura, de la que no esperamos efectos adversos comunes, pero no podemos descartar efectos de baja frecuencia. Asimismo, esperamos contar pronto con estimaciones más precisas de eficacia y seguridad (AU)

We reviewed the published evidence on the efficacy and safety of nirsevimab, a monoclonal antibody, used to prevent respiratory syncytial virus (RSV) associated lower respiratory tract infections (LRTI) in term infants. We have found a randomized double-blind placebo-controlled clinical trial that included 3012 infants, born at term or late preterm, less than one year of age with a follow-up of at least 150 days. The quality of the evidence was classified as low for very severe LRTI and moderate for LRTI requiring medical care or admission. The evidence is based on a small number of events (only 29 cases for hospital admissions, 78 for IVRB with medical care), so any estimate must be considered imprecise. Efficacy, estimated as relative risk reduction (RRR) was 76.4% (95% confidence interval [95 CI]: 62.3 to 85.2) for RSV associated LRTI that required medical care and 76.8% (CI 95: 49.4 to 89.4%) for hospital admission. No differences were found in terms of safety. There are doubts about the clinical importance, due to the severity criteria used, and about its impact, with a number needed to treat of 63 to avoid a LRTI with hospital admission and of 24 to avoid LRTI requiring medical care. Based on the available information, it seems a safe intervention, from which we do not expect common adverse effects, but we cannot rule out low-frequency effects. We also expect to have more precise estimates of efficacy and safety soon. (AU)

Reduction in the risk of progression of solid organ transplant recipients infected by SARS-CoV-2 treated with monoclonal antibodies / Reducción del riesgo de progresión en receptores de trasplantes infectados por SARS-CoV-2 tratados con anticuerpos monoclonales

Recipients of solid organ transplants (SOT) are at higher risk of infection by SARS-CoV-2 virus especially due to chronic immunosuppression therapy and frequent multiple comorbid conditions. COVID-19 is a potentially life-threatening disease in SOT recipients, with an increased likelihood of progressing to severe disease, with the need of hospitalization, admission to the intensive care unit (ICU) and mechanical ventilatory support. This article presents an updated review of different aspects related to the outcome of COVID-19 in SOT recipients. In nvaccinated SOT recipients, COVID-19 is associated with a high mortality rate, in-patient care and ICU admission, and impaired graft function or rejection in severe disease. In vaccinated SOT recipients even after full vaccination, there is a reduction of the risk of mortality, but the course of COVID-19 may continue to be severe, influenced by the time from transplant, the net state of immunosuppression and having suffered graft rejection or dysfunction. SOT recipients develop lower immunity from mRNA vaccines with suboptimal response. Treatment with mAbs provides favorable outcomes in non-hospitalized SOT recipients at high risk for severe disease, with lower rates of hospitalization, emergency department visits, ICU care, progression to severe disease, and death. However, broad vaccination and therapeutic options are required, particularly in light of the tendency of the SARS-CoV-2 virus to adapt and evade both natural

Los receptores de trasplantes de órganos sólidos (TOS) presentan un alto riesgo de infección por el virus SARS-CoV-2 debido al tratamiento inmunosupresor y múltiples comorbilidades. La COVID-19 puede ser potencialmente mortal en receptores de TOS, con un aumento de la probabilidad de progresión a enfermedad grave. Este trabajo presenta una revisión actualizada del impacto de la COVID-19 en receptores de TOS. En los receptores de TOS no vacunados, la COVID-19 se asocia con una alta tasa de mortalidad, hospitalización, ingreso en la UCI y deterioro del injerto o rechazo. En los pacientes vacunados, incluso con pauta de vacunación completa, se reduce el riesgo de mortalidad, pero el curso de la COVID-19 puede continuar siendo grave en función del tiempo desde el trasplante, el estado neto de inmunosupresión y haber sufrido rechazo o disfunción del injerto. Los receptores de TOS presentan una baja inmunogenicidad a las vacunas de ARNm y respuesta subóptima. El tratamiento con anticuerpos monoclonales (AMC) en receptores de TOS no hospitalizados con alto riesgo de enfermedad grave, se asocia con menores tasas de hospitalización, visitas a urgencias, ingreso en UCI, progresión a enfermedad grave y muerte. Sin embargo, se requieren nuevas vacunas y opciones terapéuticas, teniendo en cuenta la tendencia del virus SARS-CoV-2 a adaptarse y a evadir tanto la inmunidad natural como la inducida por la vacuna (Au)and vaccine-induced immunity (AU)

Use of monoclonal antibodies in cancer immunotherapy: types and mechanisms of action.

Immunotherapy is one of the most innovative treatments in the current field of oncology and consists of stimulating the immune system to eliminate tumoral cells. Monoclonal antibodies (mAbs) are glycoproteins secreted by B-cells capable of recognizing and neutralizing foreign organisms or antigens. Structurally, they are composed of two heavy and two light chains. The generation of therapeutic mAbs is one of the most developed and fastest-growing areas of the biotechnological and pharmaceutical industries and is an important adjunct to cancer therapy. Several antibodies have been approved for human administration and can be mouse-derived, chimeric, humanized, or fully human. mAbs main mechanism of action includes the lysis of the tumoral cells through inducing apoptosis, phagocytosis, complement activation, or signaling inhibition.

La inmunoterapia es un tratamiento innovador para la oncología actual, que consiste en la estimulación del sistema inmunitario para la eliminación de las células tumorales. Los anticuerpos monoclonales (mAbs) son glicoproteínas secretadas por los linfocitos B, capaces de reconocer y neutralizar organismos extraños o antígenos. Estructuralmente se componen de dos cadenas pesadas y dos cadenas ligeras. La generación de mAbs terapéuticos es una de las áreas de mayor crecimiento en la industria biotecnológica y farmacéutica y representa un complemento importante en la terapia del cáncer. Existen diversos mAbs que han sido aprobados para su administración en humanos, y pueden ser derivados de ratón, quiméricos, humanizados o completamente humanos. Los mecanismos de acción consisten principalmente en la lisis de las células tumorales a través de la inducción de la apoptosis, fagocitosis, activación del complemento o inhibición de la señalización celular.

Use of monoclonal antibodies in cancer immunotherapy: types and mechanisms of action / Uso de anticuerpos monoclonales en la inmunoterapia del cáncer: tipos y mecanismos de acción

Abstract Immunotherapy is one of the most innovative treatments in the current field of oncology and consists of stimulating the immune system to eliminate tumoral cells. Monoclonal antibodies (mAbs) are glycoproteins secreted by B-cells capable of recognizing and neutralizing foreign organisms or antigens. Structurally, they are composed of two heavy and two light chains. The generation of therapeutic mAbs is one of the most developed and fastest-growing areas of the biotechnological and pharmaceutical industries and is an important adjunct to cancer therapy. Several antibodies have been approved for human administration and can be mouse-derived, chimeric, humanized, or fully human. mAbs main mechanism of action includes the lysis of the tumoral cells through inducing apoptosis, phagocytosis, complement activation, or signaling inhibition.

Resumen La inmunoterapia es un tratamiento innovador para la oncología actual, que consiste en la estimulación del sistema inmunitario para la eliminación de las células tumorales. Los anticuerpos monoclonales (mAbs) son glicoproteínas secretadas por los linfocitos B, capaces de reconocer y neutralizar organismos extraños o antígenos. Estructuralmente se componen de dos cadenas pesadas y dos cadenas ligeras. La generación de mAbs terapéuticos es una de las áreas de mayor crecimiento en la industria biotecnológica y farmacéutica y representa un complemento importante en la terapia del cáncer. Existen diversos mAbs que han sido aprobados para su administración en humanos, y pueden ser derivados de ratón, quiméricos, humanizados o completamente humanos. Los mecanismos de acción consisten principalmente en la lisis de las células tumorales a través de la inducción de la apoptosis, fagocitosis, activación del complemento o inhibición de la señalización celular.

Descripción de una serie de pacientes con miastenia gravis refractaria / A series of patients with refractory myasthenia gravis

Introducción: Los avances en el tratamiento de la miastenia gravis (MG) han conseguido mejoría en la calidad de vida y el pronóstico de la mayoría de los pacientes. Sin embargo, un 10-20% presenta la denominada MG refractaria sin alcanzar mejoría, con frecuentes recaídas e importante repercusión funcional. Pacientes y métodos: Se seleccionó a pacientes con MG refractaria a partir de una cohorte de pacientes con MG diagnosticados desde enero del 2008 hasta junio del 2019. Se definió MG refractaria como falta de respuesta al tratamiento con prednisona y al menos 2 inmunosupresores o imposibilidad para la retirada del tratamiento sin recaídas en los últimos 12 meses o intolerancia al mismo con graves efectos secundarios. Resultados: Se registraron 84 pacientes con MG, 11 cumplían los criterios de MG refractaria (13%), con una edad media de 47 ± 18 años; un 64% los pacientes con MG refractaria fueron clasificados como miastenia generalizada de comienzo precoz (p < 0,01) con una mayor proporción de mujeres (p < 0,01). La gravedad de la enfermedad al diagnóstico, así como en el momento del análisis de los datos, fue superior en el grupo de MG refractaria con un mayor número de recaídas en el seguimiento. En el modelo de regresión logística se obtuvo una asociación independiente entre MG-R y el número de reagudizaciones graves. Conclusiones: El porcentaje de pacientes con MG refractaria en nuestra serie (13%) es similar al descrito en estudios previos, con frecuencia mujeres con inicio precoz, formas graves de inicio y reiteradas reagudizaciones con ingreso hospitalario en el seguimiento.(AU)

Introduction: Advances in the treatment of myasthenia gravis (MG) have improved quality of life and prognosis for the majority of patients. However, 10%-20% of patients present refractory MG, with frequent relapses and significant functional limitations. Patients and methods: Patients with refractory MG were selected from a cohort of patients diagnosed with MG between January 2008 and June 2019. Refractory MG was defined as lack of response to treatment with prednisone and at least 2 immunosuppressants, inability to withdraw treatment without relapse in the last 12 months, or intolerance to treatment with severe adverse reactions. Results: We identified 84 patients with MG, 11 of whom (13%) met criteria for refractory MG. Mean (standard deviation) age was 47 (18) years; 64% of patients with refractory MG had early-onset generalised myasthenia (as compared to 22% in the group of patients with MG; P<.01), with a higher proportion of women in this group (P<.01). Disease severity at diagnosis and at the time of data analysis was higher among patients with refractory MG, who presented more relapses during follow-up. Logistic regression analysis revealed an independent association between refractory MG and the number of severe relapses. Conclusions: The percentage of patients with refractory MG in our series (13%) is similar to those reported in previous studies; these patients were often women and presented early onset, severe forms of onset, and repeated relapses requiring hospital admission during follow-up.(AU)

A series of patients with refractory myasthenia gravis.

INTRODUCTION: Advances in the treatment of myasthenia gravis (MG) have improved quality of life and prognosis for the majority of patients. However, 10%-20% of patients present refractory MG, with frequent relapses and significant functional limitations. PATIENTS AND METHODS: Patients with refractory MG were selected from a cohort of patients diagnosed with MG between January 2008 and June 2019. Refractory MG was defined as lack of response to treatment with prednisone and at least 2 immunosuppressants, inability to withdraw treatment without relapse in the last 12 months, or intolerance to treatment with severe adverse reactions. RESULTS: We identified 84 patients with MG, 11 of whom (13%) met criteria for refractory MG. Mean (standard deviation) age was 47 (18) years; 64% of patients with refractory MG had early-onset generalised myasthenia (as compared to 22% in the group of patients with MG; P < .01), with a higher proportion of women in this group (P < .01). Disease severity at diagnosis and at the time of data analysis was higher among patients with refractory MG, who presented more relapses during follow-up. Logistic regression analysis revealed an independent association between refractory MG and the number of severe relapses. CONCLUSIONS: The percentage of patients with refractory MG in our series (13%) is similar to those reported in previous studies; these patients were often women and presented early onset, severe forms of onset, and repeated relapses requiring hospital admission during follow-up.